Active Rho (green) and actin (red) colocalize in podosomes.

Berdeaux, Díaz, and colleagues report that active Rho (Rho[GTP]) is localized to podosomes in oncogenically transformed cells (page 317). These matrix-digesting, actin-rich, short-lived protrusions help osteoclasts to eat bone and migratory and cancer cells to chew their way through matrix. Their function in Src-transformed cells is now found to rely on Rho activity.

Rho is known to promote the formation of focal adhesions and actin stress fibers, so the disappearance of stress fibers after transformation with oncogenic Src was presumed to reflect down-regulation of Rho. But Berdeaux et al. report that levels of Rho[GTP] are not decreased in Src-transformed cells. Instead, focal adhesions and stress fibers may be lost because Src induces a block in signaling downstream of Rho and a loss in cell–matrix adhesion.

Active Rho is, however, found in Src- induced podosomes. Inhibition of Rho disrupted localization of several proteins to podosomes, and almost completely abolished the secretion of matrix-digesting enzymes. Thus, Rho is necessary to form not only focal adhesions and stress fibers in normal cells but also the more dynamic and transient podosomes characteristic of transformed and tumor cells. The relevant Rho effectors are not known, but Rho may work by recruiting active Src to podosomes or by reorganizing the actin core in these structures. Several of the many signaling proteins in podosomes may, in turn, regulate the localization and activation of Rho. ▪